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Inhibitory effect of piperlonguminine on melanin production in melanoma B16 cell line by downregulation of tyrosinase expression

机译:下调酪氨酸酶表达对哌隆丁胺对黑色素瘤B16细胞黑色素生成的抑制作用

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摘要

Tyrosinase is a key enzyme for melanin biosynthesis, and hyperpigmentation disorders are associated with abnormal accumulation of melanin pigments, which can be improved by treatment with depigmenting agents. In the present study, piperlonguminine from Piper longum was discovered to inhibit melanin production in melanoma B16 cells stimulated with alpha-melanocyte stimulating hormone (alpha-MSH), 3-isobutyl-1-methylxanthine or protoporphyrin IX, where the compound exhibited stronger depigmenting efficacy than kojic acid. However, piperlonguminine did not affect 1-oleoyl-2-acetyl-sn-glycerol-induced melanogenesis and did not affect protein kinase C-mediated melanin production. Surprisingly, piperlonguminine did not inhibit the catalytic activity of cell-free tyrosinase from melanoma B16 cells but rather suppressed tyrosinase mRNA expression. This effect was attributed to the inhibitory action of piperlonguminine on alpha-MSH-induced signaling through cAMP to the cAMP responsive element binding protein that in turn regulates the expression of the microphthalmia-associated transcription factor, a key activator of the tyrosinase promoter. This study demonstrates that piperlonguminine is an efficient depigmenting agent with a novel mechanism of action.
机译:酪氨酸酶是黑色素生物合成的关键酶,色素沉着过度与黑色素色素的异常蓄积有关,可以通过用色素沉着剂治疗来改善色素沉着。在本研究中,发现从长胡椒中得到的胡椒基丁胺抑制了用α-黑素细胞刺激激素(α-MSH),3-异丁基-1-甲基黄嘌呤或原卟啉IX刺激的黑色素瘤B16细胞中的黑色素生成,该化合物表现出更强的脱色素功效比曲酸。但是,哌丁胺不影响1-油酰基-2-乙酰基-sn-甘油诱导的黑色素生成,也不影响蛋白激酶C介导的黑色素生成。令人惊奇的是,哌隆丁宁不抑制来自黑素瘤B16细胞的无细胞酪氨酸酶的催化​​活性,而是抑制酪氨酸酶mRNA的表达。该作用归因于哌隆丁胺对α-MSH诱导的信号的抑制作用,通过cAMP传递给cAMP响应元件结合蛋白,而cAMP响应元件结合蛋白又调节了与小眼科相关的转录因子(酪氨酸酶启动子的关键激活因子)的表达。这项研究表明,哌隆宁是一种具有新型作用机理的高效脱色剂。

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